Drug Discovery Studies in BTBR Mouse Model of Autism Spectrum Disorder
The BTBR T+tf/J mouse model has been reported to exhibit several symptoms of ASD, including reduced social interactions and anxiety compared to other inbred strains. Additionally, the brain anatomy in this mouse model has previously revealed profound abnormalities compared to regular strains, such as C57Bl/6J mice.
Charles River scientists characterized the BTBR T+tf/J mouse model using behavioral studies and noninvasive imaging to validate its utility for drug discovery of ASD therapies. BTBR T+tf/J mice exhibited:
- Impairment in the rotarod test, a measure of motor behavior
- Decreased whole brain and striatum volumes, and statistical variation in metabolite levels
- Increased horizontal activity in the open field locomotor test
- Less freezing behavior in the contextual fear conditioning test
The brain anatomy and metabolic profile were assessed using MRI and 1H-MRS imaging, respectively. The imaging data was complemented by histological and biochemical tools to assess ASD-related markers. Taken together, the behavior tests and imaging data support the utility of the BTBR T+tf/J mice for ASD preclinical studies.